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The Oncologist May 2007Like nearly all systemic cancer therapies, monoclonal antibodies are associated with hypersensitivity reactions. This article reviews the characteristics and management... (Review)
Review
BACKGROUND
Like nearly all systemic cancer therapies, monoclonal antibodies are associated with hypersensitivity reactions. This article reviews the characteristics and management of hypersensitivity reactions to monoclonal antibodies and commonly used chemotherapy agents.
METHODS
MEDLINE was searched for recent studies and reviews pertaining to hypersensitivity reactions with monoclonal antibodies (cetuximab, rituximab, trastuzumab, panitumumab, bevacizumab), platinum compounds (carboplatin, oxaliplatin), and taxanes (paclitaxel, docetaxel). Emphasis was placed on articles that provided practical information on hypersensitivity reaction management. Data found in the literature were supplemented with information from the package insert for each agent.
RESULTS
Severe hypersensitivity reactions are rare, with an incidence of < or =5%, provided patients receive proper premedication, close monitoring, and prompt intervention when symptoms occur. Hypersensitivity reactions to platinum compounds are generally consistent with type 1 hypersensitivity, occurring after multiple cycles of therapy. Reactions to taxanes and monoclonal antibodies produce similar symptoms, but are generally immediate, occurring during the first few minutes of the first or second infusion. However, 10%-30% of reactions to monoclonal antibodies are delayed, and may occur in later infusions, indicating the importance of close observation of the patient following administration. Mild-to-moderate reactions can be managed by temporary infusion interruption, reduction of the infusion rate, and symptom management. Rechallenge should be considered after complete resolution of all symptoms. Severe reactions may require treatment discontinuation.
CONCLUSION
Hypersensitivity or infusion reactions to platinum compounds are acquired; reactions to taxanes and monoclonal antibodies are immediate and typically occur during the first few minutes of the first infusion. The different time of onset should be considered when developing strategies for preventing and managing hypersensitivity reactions. The decision to rechallenge or discontinue treatment after a reaction occurs depends on the severity of the reaction and other clinical factors.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Immunologic Factors; Incidence; Infusions, Intravenous; Platinum Compounds; Taxoids; Time Factors
PubMed: 17522249
DOI: 10.1634/theoncologist.12-5-601 -
Current Problems in Dermatology 2015Tattoos cause a broad range of clinical problems. Mild complaints, especially sensitivity to sun, are very common and seen in 1/5 of cases. Medical complications are... (Review)
Review
Tattoos cause a broad range of clinical problems. Mild complaints, especially sensitivity to sun, are very common and seen in 1/5 of cases. Medical complications are dominated by allergy to tattoo pigment haptens or haptens generated in the skin, especially in red tattoos but also in blue and green tattoos. Symptoms are major and can be compared to cumbersome pruritic skin diseases. Tattoo allergies and local reactions show distinct clinical manifestations, with plaque-like, excessive hyperkeratotic, ulcero-necrotic, lymphopathic, neuro-sensory, and scar patterns. Reactions in black tattoos are papulo-nodular and non-allergic and associated with the agglomeration of nanoparticulate carbon black. Tattoo complications include effects on general health conditions and complications in the psycho-social sphere. Tattoo infections with bacteria, especially staphylococci, which may be resistant to multiple antibiotics, may be prominent and may progress into life-threatening sepsis. Contaminated tattoo ink is an open-window risk vector that can lead to epidemic tattoo infections across national borders due to contaminated bulk production. Hepatitis B and C and human immunodeficiency virus (HIV) transferred by tattooing remain a significant risk needing active prevention. It is noteworthy that cancer arising in tattoos, in regional lymph nodes, and in other organs due to tattoo pigments and ingredients has not been detected or noted as a significant clinical problem hitherto, despite millions of people being tattooed for decennia. Clinical observation and epidemiology disagree with register data, which indicate an increased risk of cancer due to chemical carcinogens present in some inks. Registers rely on chronic dosaging of cell lines and animals. However, tattooing in humans is essentially a single-dose exposure, which might explain the observed discrepancy.
Topics: Cicatrix; Color; Coloring Agents; Humans; Hypersensitivity, Delayed; Photosensitivity Disorders; Skin Diseases, Bacterial; Tattooing; Urticaria; Virus Diseases
PubMed: 25833625
DOI: 10.1159/000369645 -
International Archives of Allergy and... 2016Delayed drug allergy reactions (DDAR) are potentially fatal. Certain human leukocyte antigen (HLA) alleles have been associated with delayed allergy reactions following... (Review)
Review
Delayed drug allergy reactions (DDAR) are potentially fatal. Certain human leukocyte antigen (HLA) alleles have been associated with delayed allergy reactions following the administration of particular drugs. Examples are HLA-B*57:01 (abacavir), HLA-B*15:02/HLA-A*31:01 (carbamazepine), and HLA-B*58:01 (allopurinol). Based on the identification of these associations, it may now be possible to prevent certain allergy reactions that were, until recently, considered unpredictable. In this review, we will focus on the pharmacogenetics of the best-studied associations between specific HLA alleles and delayed allergy reactions and describe the pathogenesis models proposed so far. Finally, we will evaluate the genetic screening strategies available and discuss the clinical relevance of a better understanding of the immunogenetics and mechanisms involved in DDAR.
Topics: Alleles; Anticonvulsants; Antiviral Agents; Disease Susceptibility; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; Female; Genetic Testing; HLA Antigens; Haptens; Humans; Hypersensitivity, Delayed; Male; Odds Ratio; Receptors, Immunologic; Stevens-Johnson Syndrome; Virus Diseases; Viruses
PubMed: 27576480
DOI: 10.1159/000448217 -
Actas Dermo-sifiliograficas Mar 2016Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce... (Review)
Review
Corticosteroids are widely used drugs in the clinical practice, especially by topic application in dermatology. These substances may act as allergens and produce immediate and delayed hypersensitivity reactions. Allergic contact dermatitis is the most frequent presentation of corticosteroid allergy and it should be studied by patch testing in specific units. The corticosteroids included in the Spanish standard battery are good markers but not ideal. Therefore, if those makers are positive, it is useful to apply a specific battery of corticosteroids and the drugs provided by patients. Immediate reactions are relatively rare but potentially severe, and it is important to confirm the sensitization profile and to guide the use of alternative corticosteroids, because they are often necessary in several diseases. In this article we review the main concepts regarding these two types of hypersensitivity reactions in corticosteroid allergy, as well as their approach in the clinical practice.
Topics: Adrenal Cortex Hormones; Allergens; Dermatitis, Allergic Contact; Humans; Hypersensitivity, Delayed; Patch Tests
PubMed: 26621334
DOI: 10.1016/j.ad.2015.09.012 -
Swiss Medical Weekly Feb 2023Corticosteroids, which are anti-inflammatory and immunosuppressive agents used for the treatment of various diseases including allergic disorders, can induce immediate... (Review)
Review
BACKGROUND
Corticosteroids, which are anti-inflammatory and immunosuppressive agents used for the treatment of various diseases including allergic disorders, can induce immediate and delayed hypersensitivity reactions. Although these reactions are not common, due to the wide usage of corticosteroid medications, corticosteroid hypersensitivity reactions are clinically important.
OBJECTIVE
In this review, we summarise the prevalence, pathogenetic mechanism, clinical manifestations, risk factors, diagnostic and therapeutic approach for corticosteroid-induced hypersensitivity reactions.
METHODS
An integrative review of the literature was conducted using PubMed searches (mainly large cohort-based studies) regarding the different aspects of corticosteroid hypersensitivity.
RESULTS
Hypersensitivity reactions to corticosteroids can be immediate or delayed and can follow all modes of corticosteroid administration. Prick and intradermal skin tests are useful diagnostic tools for immediate hypersensitivity reactions, patch tests are useful for delayed hypersensitivity reactions. According to the diagnostic tests an alternative (safe) corticosteroid agent should be administered.
CONCLUSION
Physicians of all medical disciplines should be aware that corticosteroids can cause (paradoxically) immediate or delayed allergic hypersensitivity reactions. The diagnosis of such allergic reactions is challenging since it is often difficult to distinguish between hypersensitivity reactions and deterioration of the basic inflammatory disease (e.g., worsening of asthma or dermatitis). Thus, a high index of suspicion is needed in order to identify the culprit corticosteroid.
Topics: Humans; Prevalence; Drug Hypersensitivity; Adrenal Cortex Hormones; Hypersensitivity, Immediate; Hypersensitivity, Delayed; Skin Tests
PubMed: 36800886
DOI: 10.57187/smw.2023.40025 -
International Journal of Molecular... Feb 2019There is an increasing demand for alternative in vitro methods to replace animal testing, and, to succeed, new methods are required to be at least as accurate as... (Review)
Review
There is an increasing demand for alternative in vitro methods to replace animal testing, and, to succeed, new methods are required to be at least as accurate as existing in vivo tests. However, skin sensitization is a complex process requiring coordinated and tightly regulated interactions between a variety of cells and molecules. Consequently, there is considerable difficulty in reproducing this level of biological complexity in vitro, and as a result the development of non-animal methods has posed a major challenge. However, with the use of a relevant biological system, the high information content of whole genome expression, and comprehensive bioinformatics, assays for most complex biological processes can be achieved. We propose that the Genomic Allergen Rapid Detection (GARD™) assay, developed to create a holistic data-driven in vitro model with high informational content, could be such an example. Based on the genomic expression of a mature human dendritic cell line and state-of-the-art machine learning techniques, GARD™ can today accurately predict skin sensitizers and correctly categorize skin sensitizing potency. Consequently, by utilizing advanced processing tools in combination with high information genomic or proteomic data, we can take the next step toward alternative methods with the same predictive accuracy as today's in vivo methods-and beyond.
Topics: Genomics; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Machine Learning; Skin Tests
PubMed: 30720708
DOI: 10.3390/ijms20030666 -
European Annals of Allergy and Clinical... Jul 2021Different clinical pictures are related to corticosteroids (CS) non immediate hypersensitivity and the frequency of these reactions can be underestimated. The...
Different clinical pictures are related to corticosteroids (CS) non immediate hypersensitivity and the frequency of these reactions can be underestimated. The classification of CS in 3 groups and the identification of two patient's profiles has been proposed by Baeck to help clinicians in the management of these cases. Data of 14 patients with clinical history of delayed reactions to various CS and positive skin test and/or oral challenge are retrospectively analyzed. Three different patterns of patients are identified evaluating history, clinical picture and tests results. The first one (6 pts, 43%) is characterized by cutaneous and/or mucosal reaction due to inhaled Budesonide and patch test positive only to topical molecules belonging to the group 1 of CS. The second pattern (4 pts) has clinical history of local and systemic skin reactions to the topic and parenteral administration of the same or other steroid drugs. Patients belonging to the third pattern (4 pts) have a history of systemic reactions to general administration of CS without previous contact reaction. Pattern 2 and 3 show a wide sensitization to molecules belonging to the 3 groups of CS. All the patients show patch test positive to Budesonide. Although the lack of standardization, the allergy workup proves useful to differentiate patients sensitized to one or few molecules from polysensitized and to identify the culprit drugs. Intradermal and challenge test are necessary to complete the diagnostic workup. The results suggest the possibility of a different management of patients. Patients of pattern one can be only patch tested with a limited series of CS belonging to the 3 groups. They don't need an extensive exclusion of steroids use. The pattern 2 and 3 must be submitted instead to a complete allergological individual evaluation to identify alternative tolerated drugs, because of the risk of systemic reactions. The Baeck's classification shows limited usefulness in these cases.
Topics: Adrenal Cortex Hormones; Adult; Budesonide; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Patch Tests; Retrospective Studies; Young Adult
PubMed: 32729318
DOI: 10.23822/EurAnnACI.1764-1489.164 -
International Journal of Molecular... Jun 2017Drug hypersensitivity reactions have multiple implications for patient safety and health system costs, thus it is important to perform an accurate diagnosis. The... (Review)
Review
Drug hypersensitivity reactions have multiple implications for patient safety and health system costs, thus it is important to perform an accurate diagnosis. The diagnostic procedure includes a detailed clinical history, often unreliable; followed by skin tests, sometimes with low sensitivity or unavailable; and drug provocation testing, which is not risk-free for the patient, especially in severe reactions. In vitro tests could help to identify correctly the responsible agent, thus improving the diagnosis of these reactions, helping the physician to find safe alternatives, and reducing the need to perform drug provocation testing. However, it is necessary to confirm the sensitivity, specificity, negative and positive predictive values for these in vitro tests to enable their implementation in clinical practice. In this review, we have analyzed these parameters from different studies that have used in vitro test for evaluating drug hypersensitivity reactions and estimated the added value of these tests to the in vivo diagnosis.
Topics: Diagnostic Tests, Routine; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunoglobulin E; T-Lymphocytes
PubMed: 28590437
DOI: 10.3390/ijms18061222 -
Clinical Reviews in Allergy & Immunology Jun 2022Confirming drug imputability is an important step in the management of cutaneous adverse drug reactions (CADR). Re-challenge is inconvenient and in many cases life... (Review)
Review
Confirming drug imputability is an important step in the management of cutaneous adverse drug reactions (CADR). Re-challenge is inconvenient and in many cases life threatening. We review the literature on ideal patch testing technique for specific CADRs. Testing should be performed approximately 3 months after the resolution of the eruption using standard patch testing techniques. Commercially available patch test preparations are available for a minority of drugs, so in most cases, testing should be performed with the drug at various recommended concentrations and in different vehicles. Testing to all known excipients, such as dyes, vehicles and preservatives is also important. Immunosuppressive medications should be discontinued or down titrated to the lowest tolerable dose to decrease the risk of false negative reactions. We provide an overview of expert recommendations and extant evidence on the utility of patch testing for identifying the culprit drug in common CADRs and for specific drug or drug classes. Overall, there appears to be significant variability in the patch test positivity of different drugs, which is likely the result of factors intrinsic to the drug such as dermal absorption (as a function of lipophilicity and molecular size) and whether the drug itself or a downstream metabolite is implicated in the immune reaction. Drugs with high patch test positivity rates include beta-lactam antibiotics, aromatic anticonvulsants, phenytoin, and corticosteroids, among others. Patch testing positivity varies both as a function of the drug and type of CADR. The sum of the evidence suggests that patch testing in the setting of morbilliform eruptions, fixed drug eruption, acute generalized exanthematous pustulosis, and possibly also drug-induced hypersensitivity syndrome, photoallergic and eczematous reactions may be worthwhile, although utility of testing may vary on the specific drug in question for the eruption. It appears to be of limited utility and is not recommended in the setting of other complex CADR, such as SJS/TEN and leukocytoclastic vasculitis.
Topics: Anticonvulsants; Drug Eruptions; Drug Hypersensitivity; Exanthema; Humans; Hypersensitivity, Delayed; Patch Tests
PubMed: 35113364
DOI: 10.1007/s12016-022-08924-2 -
Journal of Investigational Allergology... 2020The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions... (Review)
Review
The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions (DHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of DHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to perform a literature review on allergy to pharmaceutical excipients and to record the DHRs described with various types of medications, specifically due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient, in order to obtain a list of the excipients most frequently involved for each type of medication.
Topics: Disease Management; Disease Susceptibility; Drug Compounding; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Excipients; Humans; Hypersensitivity, Delayed; Pharmaceutical Preparations
PubMed: 32376520
DOI: 10.18176/jiaci.0562